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An ultra-small-area, low-power analog front-end (AFE) for high-density neural recording is presented in this paper. It features an 11-bit incremental delta-sigma analog-to-digital converter (σ ADC) enhanced with an offset-rejecting event-driven input biasing network. This network avoids saturation of the ADC input caused by leakage of the input-coupling capacitor implemented in an advanced technology node. Combining AC-coupling with direct data conversion, the proposed AFE can tolerate a rail-to-rail electrode offset and achieves a good trade-off between power, noise, bandwidth, input impedance, and area. Fabricated in a 22-nm fully-depleted silicon on insulator (FDSOI) process, the design occupies an active area of

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the "3R" principle of "Refining, Reducing and Replacing" animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models. Among the animal-free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal-free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non-animal-based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal-free approaches. ispartof: EMBO JOURNAL vol:41 issue:6 ispartof: location:England status: published

Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics paradigm, especially in biomedical research. Recreating artificial life-like actuation dynamics is crucial for a soft-robotic system. However, the precise control and tuning of actuation behavior still represents one of the main challenges of modern soft robotic systems. This method describes a low-cost, highly scalable, and easy-to-use procedure to fabricate an electrically controllable soft robot with life-like movements that is activated and controlled by the contraction of cardiac muscle tissue on a micropatterned sting ray-like hydrogel scaffold. The use of soft photolithography methods makes it possible to successfully integrate multiple components in the soft robotic system, including micropatterned hydrogel-based scaffolds with carbon nanotubes (CNTs) embedded gelatin methacryloyl (CNT-GelMA), poly(ethylene glycol) diacrylate (PEGDA), flexible gold (Au) microelectrodes, and cardiac muscle tissue. In particular, the hydrogels alignment and micropattern are designed to mimic the muscle and cartilage structure of the sting ray. The electrically conductive CNT-GelMA hydrogel acts as a cell scaffold that improves the maturation and contraction behavior of cardiomyocytes, while the mechanically robust PEGDA hydrogel provides structural cartilage-like support to the whole soft robot. To overcome the hard and brittle nature of metal-based microelectrodes, we designed a serpentine pattern that has high flexibility and can avoid hampering the beating dynamics of cardiomyocytes. The incorporated flexible Au microelectrodes provide electrical stimulation across the soft robot, making it easier to control the contraction behavior of cardiac tissue.

The skin is the largest and most exposed organ in the human body. Not only it is involved in numerous biological processes essential for life but also it represents a significant endpoint for the application of pharmaceuticals. The area of in vitro skin tissue engineering has been progressing extensively in recent years. Advanced in vitro human skin models strongly impact the discovery of new drugs thanks to the enhanced screening efficiency and reliability. Nowadays, animal models are largely employed at the preclinical stage of new pharmaceutical compounds development for both risk assessment evaluation and pharmacokinetic studies. On the other hand, animal models often insufficiently foresee the human reaction due to the variations in skin immunity and physiology. Skin-on-chips devices offer innovative and state-of-the-art platforms essential to overcome these limitations. In the present review, we focus on the contribution of skin-on-chip platforms in fundamental research and applied medical research. In addition, we also highlighted the technical and practical difficulties that must be overcome to enhance skin-on-chip platforms, e.g. embedding electrical measurements, for improved modeling of human diseases as well as of new drug discovery and development.

Neurodegenerative disorders are related to the progressive functional loss of the brain, often connected to emotional and physical disability and, ultimately, to death. These disorders, strongly connected to the aging process, are becoming increasingly more relevant due to the increase of life expectancy. Current pharmaceutical treatments poorly tackle these diseases, mainly acting only on their symptomology. One of the main reasons of this is the current drug development process, which is not only expensive and time-consuming but, also, still strongly relies on animal models at the preclinical stage.:Organ-on-a-chip platforms have the potential to strongly impact and improve the drug screening process by recreating in vitro the functionality of human organs. Patient-derived neurons from different regions of the brain can be directly grown and differentiated on a brain-on-a-chip device where the disease development, progression and pharmacological treatments can be studied and monitored in real time. The model reliability is strongly improved by using human-derived cells, more relevant than animal models for pharmacological screening and disease monitoring. The selected cells will be then capable of proliferating and organizing themselves in the in vivo environment thanks to the device architecture, materials selection and bio-chemical functionalization.:In this review, we start by presenting the fundamental strategies adopted for brain-on-a-chip devices fabrication including e.g., photolithography, micromachining and 3D printing technology. Then, we discuss the state-of-theart of brain-on-a-chip platforms including their role in the study of the functional architecture of the brain e.g., blood-brain barrier, or of the most diffuse neurodegenerative diseases like Alzheimer’s and Parkinson’s. At last, the current limitations and future perspectives of this approach for the development of new drugs and neurodegenerative diseases modeling will be discussed.

To create life-like movements, living muscle actuator technologies have borrowed inspiration from biomimetic concepts in developing bioinspired robots. Here, the development of a bioinspired soft robotics system, with integrated self-actuating cardiac muscles on a hierarchically structured scaffold with flexible gold microelectrodes is reported. Inspired by the movement of living organisms, a batoid-fish-shaped substrate is designed and reported, which is composed of two micropatterned hydrogel layers. The first layer is a poly(ethylene glycol) hydrogel substrate, which provides a mechanically stable structure for the robot, followed by a layer of gelatin methacryloyl embedded with carbon nanotubes, which serves as a cell culture substrate, to create the actuation component for the soft body robot. In addition, flexible Au microelectrodes are embedded into the biomimetic scaffold, which not only enhance the mechanical integrity of the device, but also increase its electrical conductivity. After culturing and maturation of cardiomyocytes on the biomimetic scaffold, they show excellent myofiber organization and provide self-actuating motions aligned with the direction of the contractile force of the cells. The Au microelectrodes placed below the cell layer further provide localized electrical stimulation and control of the beating behavior of the bioinspired soft robot.

Despite the current progresses of modern medicine, the resistance of malignant tumors to present medical treatments points to the necessity of developing new therapeutic approaches. In recent years, numerous studies have focused their attention on the promising use of nanomaterials, like iron oxide nanowires, zinc oxide or mesoporous silica nanoparticles, for cancer and metastasis treatment with the advantage of operating directly at the bio-molecular scale. Among them, carbon nanotubes emerged as valid candidates not only for drug delivery, but also as a valuable tool in cancer imaging and physical ablation. Nevertheless, deep investigations about carbon nanotubes’ potential bio-compatibility and cytotoxicity limits should be also critically addressed. In the present review, after introducing carbon nanotubes and their promising advantages and drawbacks for fighting cancer, we want to focus on the numerous and different ways in which they can assist to reach this goal. Specifically, we report on how they can be used not only for drug delivery purposes, but also as a powerful ally to develop effective contrast agents for tumors’ medical or photodynamic imaging, to perform direct physical ablation of metastasis, as well as gene therapy.

The sensing capabilities of zinc oxide nano/micro-structures have been widely investigated and these structures are frequently used in the fabrication of cutting-edge sensors. However, to date, little attention has been paid to the multi-sensing abilities of this material. In this work, we present an efficient multisensor based on a single zinc oxide microwire/gold junction. The device is able to detect in real time three different stimuli, UV-VIS light, temperature and pH variations. This is thanks to three properties of zinc oxide its photoconductive response, pyroelectricity and surface functionalization with amino-propyl groups, respectively. The three stimuli can be detected either simultaneously or in a sequence/random order. A specific mathematical tool was also developed, together with a design of experiments (DoE), to predict the performances of the sensor. Our micro-device allows reliable and versatile real-time measurements of UV-VIS light, temperature and pH variations. Therefore, it shows great potential for use in the field of sensing for living cell cultures.

This work proposes a low-cost and easy-to-fabricate sensor based on single ZnO nanowire (ZnO-NW) assembled by dielectrophoresis (DEP) onto gold nanogap electrodes. Thanks to the widespread sensing properties of ZnO-NWs, the fabricated device can be used to monitor in real-time the UV-light. DC measurements have shown a Schottky-like I–V characteristic which varies depending on the UV light intensity. The AC analysis of the ZnO-NW electrical properties has also shown impedance variations proportional to the UV irradiance. In particular, the reported measurements show high sensitivity to low UV irradiance (below 1mW/cm2) translated to both resistive and capacitive variations. Thanks to the low-cost assembly process, the proposed nanowire-on-nanogap-based sensor can be considered a preliminary step to characterize nanomaterials before assembling them onto CMOS technology, opening the field to the Micro-for-Nano approach, i.e. an electronic circuit platform to integrate nanostructured materials and read-out their sensing parameters.

deficit in motor unit recruitment. Moreover, in comparison with the control group, the total work at 180 deg/sec (-55%) and the average muscular power (-45%) were significantly impaired. The higher deficit of the flexors compared with the extensors may be related to both the hypertonicity rate of the quadriceps and disturbances of reciprocal inhibition time during the alternate movement. From a morphological point of view it appears as a deficit in the muscle tension development in the initial part of the flexion curve. Our results, in contrast, do not show significant differences between the two groups in relation to endurance ratio and work recovery. This is in contrast to the increased fatigability commonly reported by MS patients. The